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| January 11, 2010 | | New drug may help reduce muscle damage caused by heart attack | | London: An international team of researchers have discovered a potential therapeutic target that could help reduce muscle damage caused by heart attacks. They have explained how a "chemical
chaperone" does its job in the body. The new class of drugs would work by restoring
the activity of a mutated enzyme, rather than taking the more common approach
of blocking the actions of a disease-related protein. Lead researchers Dr Thomas
Hurley, from Indiana University, and Dr Daria Mochly-Rosen, from Stanford University
discovered a compound called Alda-1, which acts much like a shim to prop up a
mutated form of a key enzyme, restoring the enzyme's function. The enzyme, called
ALDH2, plays an important role in metabolizing alcohol and other toxins, including
those created by a lack of oxygen in the wake of a heart attack. It also is involved
in the metabolism of nitroglycerin, which is used to prevent chest pain (angina)
caused by restricted blood flow and oxygen to the heart. Alda-1 activates the
ALDH2 enzyme in a process that the researchers liken to a woodworking procedure
in which Alda-1 attaches to the ALDH2 enzyme at a crucial spot and acts like a
shim or wedge to prop it up. "Because of the mutation in the gene, parts of the
protein structure become loose and floppy. Alda-1 reactivates the enzyme by propping
up those parts of the structure so they regain normal function," Nature magazine
quoted Hurley as saying. He said determining how the Alda-1 compound works will
enable the researchers to begin working on alternative compounds that hold more
promise as potential drugs. One primary improvement needed is the ability to give
the drug orally, rather than by injection, he added. The study appears in Nature
Structural Biology. |
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